Several medical conditions could potentially be treated more effectively by local administration of therapeutic agents. Recent Studies of the biology of arterial wall have clarified the nature of several localized pathologic changes in the intima, which could be treated effectively with local administration of variety of pharmacologic agents, for example:                the vulnerable plaque (an atherosclerotic lesion, with high probability of rapid evolution into total occlusion, resulting in dependent tissue death), and        the restenosis lesions (the fibro cellular proliferative response to the trauma caused by angioplasty interventions onto the vascular wall, leading to recurrent blockage of treated vessel).        
Active biological processes in a localizable segment of the circulation can potentially be addressed by local administration of active pharmacologic agents more effectively than by systemic administration route. Both the tissue concentration that can be reached by local delivery and the avoidance of systemic toxicity, besides the diminished dose and cost of the active drug and quickness of its effect, all play in favor of a local administration.
Several alternative methods of local administration of drugs into the desired arterial wall have been developed and tested, namely:                Endoluminal injection. Catheters have been devised that could obviate to the ineffectiveness of just endo-luminal infusion, while the blood circulation is maintained like temporary double balloon catheter realizing the isolation of the target vascular segment; side-holes injection through especially designed balloons (leaky balloons) or coiled tubing; needle-balloons that are inflated by the same liquid/pressure that is used to inject the active ingredient by the use of communicating needles; and others.        
Klein et al. in U.S. Pat. No. 5,810,767 describe one such device where network of tubules attached onto an angioplasty type balloon. The tiny holes in the tubular network would carry the drug to the target region for drug therapy. This type of system obviously blocks the flow of blood distal to the target region and therefore can cause major problems to the patient due to ischemic manifestations.
Hanson et al. in U.S. Pat. No. 5,985,307 also describe a means to deliver drugs by binding the drug to a balloon like device which when inflated or located in the target area will allow the drug to diffuse into the vessel wall, also requiring the stoppage of the flow of fluids in the lumen.
Reed et al. in U.S. Pat. No. 6,97,013 B1, describe a balloon like device containing an array of needles that are affixed to the surface of the balloon. When the balloon is inflated, the needles will puncture into the vessel wall and the pharmacological agents are injected into the wall using the fluid agent to inflate the balloon. These devices are very bulky and are difficult to manipulate into small arteries of the heart. They need to be collapsed when the device is moved within the vessels and the procedure is very cumbersome. And if the device is not collapsed when it is advanced or withdrawn, the device can cause substantial damage to the vessel wall.
Young et al. in U.S. Pat. No. 5,788,673 describe a syringe device for controlling the rate of drug infusion systemically but provides no means to inject the drugs into the vessel wall.
Harrison et al. in U.S. Pat. No. 5,554,119, also describe a balloon like tubular device having tiny holes that would allow the infusion of the pharmacologic agents into the lumen of the vessel. Here again, the drug is easily washed away by the blood stream before it can get diffused into the vessel wall. These devices also tend to be bulky and are quite ineffective in getting the drugs into the luminal wall.
Levy et al. in U.S. Pat. No. 5,833,658 describe another balloon type device where a collar of the balloon allows flooding the pharmacologic or other agents in a vascular segment, where they can diffuse into the vessel wall. Again these types of devices occlude the flow of blood in the lumen during such procedures, which often require long periods for the diffusion of the drugs. As such they are highly ineffective. Schweich et al. in U.S. Pat. No. 5,558,642 describes a similar concept.
Schreiner in U.S. Pat. No. 5,904,670 describes a device that expands once deployed in the vessel due to shape memory characteristics. The device contains needles that can puncture into the vessel wall. While this device allows blood flow during the procedure as compared to other devices that contain a balloon, these wire cages are very cumbersome to use and the orientation of the needles is difficult to maintain, in a biological environment, where often the vessels are tortuous and non linear. Also the push-pull mechanisms that drive the needle assemblies often do not provide sufficient puncture force to puncture the intimal layers and are highly ineffective.
Jacobsen et al. describe a device in their U.S. Pat. No. 6,302,870 that has a group of retractable needles that can be made to project out of a catheter having collars to stop the penetration of the needle. The disadvantages of this design are that often it is impractical to slide a group of tubes with a small catheter tube whose overall diameter is less than 1.5 mm and it is also impractical to be able to stop the penetration of a needle with the use of a tiny needle using a collar whose diameter is only slightly larger than the needle itself. Jacobsen et al. also describe an apparatus in which the needles protrude out of a tube by the use of a twisting motion, however in order to obtain sufficient outward movement, the enclosed length has to be fairly large making the tube diameter very large causing the blockage of the lumen and making the device bulky. Additionally, there is no means to control the depth of penetration of the needles into the vessel wall.
Others, such as Haim, U.S. Pat. No. 6,254,573, on the other hand, have developed various means of injecting the drug to the wall of the blood vessel using metallic and non-metallic needles of various sizes and shapes. Although this method does not necessarily block the blood flow to the organ, actually constructing such a device that can accomplish this objective, is not easily done. The metallic “needles” are stiff and difficult to manage and the actual penetration of the needle into the vessel wall cannot be easily controlled. On the other hand “needles” made from plastics and other non-metallic materials often do not have sufficient strength and orientation to penetrate the vessel wall adequately. Any device containing a metallic needle, however small in diameter, tends to make the catheter stiff and not tractable, hence, clinically unusable.
Glines et.al. U.S. Pat. No. 6,183,444, have developed “Drug Delivery Module”—type system having a needle attached to a reservoir that is delivered using an endoscope or a catheter. Ahem et.al. U.S. Pat. No. 6,251,418 suggests a method of implanting pellets containing the drug in the myocardial tissue.
Still other inventors, such as Ungs, U.S. Pat. No. 6,149,641, have devised other means such as impregnating the drug into a carrier medium or using a porous balloon where by the drug bleeds out of the porous balloon. Winkler et.al. U.S. Pat. No. 6,200,257 discuss other methods such as a drug, placed in a hydrophilic medium, which is bonded on to the outside surface of a delivery device such as a balloon catheter or stent. Such placement of the drug can vary from just a physical mix to a covalent bond to the hydro-gel itself.
Special devices have been designed in order to access percutaneously the pericardium and then to deliver pharmacologic agents in the pericardial cavity, which is in close contact with the sub-epericardial coronary arteries. None of the above methods or devices, known as pericardial injection, have achieved clinical acceptance.
Igo et al. in U.S. Pat. No. 5,643,895, describes a method for injecting various liquid agents into the pericardium however such methods have very little chance of providing the correct amount of the agent into the target area to be effective, since they depend on diffusion in a large pericardial cavity where fluid is continuously produced and absorbed.
Recently, the technology has been perfected to cover vascular stents (metallic endovascular prosthesis) with special coatings, able to carry and then deliver (small) doses of drugs. Cordis/Johnson & Johnson produce a stent featuring polymer coating carrying small quantities of sirolimus, an anti-proliferative drug. Specifically, such stents are been evaluated to treat or prevent restenosis in stents used for coronary angioplasty. Several drugs and genetically engineered products (potentially, also virus-mediated nuclear transfusion of altered DNA material) are being tested for local delivery. The following intrinsic features potentially limit the coated/medicated stent technology: They need to be developed as a unit of stent/coating/drug, in a complex and expensive process; medicated stents provide limited amount of drugs; medicated stents can only deliver the drugs over a limited time, possibly by chemical gradient migration, or diffusion at the external wall of the stent; the active principle may have variable migration capacity, depending on the arterial wall anatomic features (fibrotic capsule, cholesterol or calcium deposits) or cellular composition (especially, concentration of macrophages); and the necessary utilization of stents, to carry the active drugs. Such active drugs may be more effective (and economical) in the absence of a stent. In the case of in-stent restenosis (recurrent obstruction, inside a previously installed stent), the use of stent inside prior stents increases the probability of new recurrence of obstruction. Additionally, it is likely that many lesions commonly treated at the present time with a stent without drug coating, may have a better and more economical result by use of stent alone and balloon angioplasty when accompanied by effective anti-proliferative medication.
For all these reasons it is believed that a specially designed device, that can reliably inject, subintimally, adequate amounts of pharmacologic agents, could improve the results of angioplasty, while limiting the cost of the intervention. It must be noted that, the absolute amount of scar tissue caused by stents is much larger than the scarring caused by stand-alone balloon angioplasty. It is the larger inner lumen that can be generally achieved with stents that can compensate for the increased scarring.